Effects And Influence On Glucose Metabolism Of Replacement Therapy With Domestic Recombinant Human Growth Hormone In Children With Growth Hormone Deficiency

Objective Growth hormone deficiency(GHD) is the important cause of short stature in children and GH-replacement therapy has been recommended for treatment of GHD. Growth hormone has well known antiinsulin effects. The few trials that have investigated the effects of GH replacement therapy on glucose metabolism and pancreatic beta-cell function in GHD children have shown conflicted results. In this study, we evaluate the efficacy of treatment and influence on glucose metabolism with domestic recombinant human growth hormone( rhGH) in children with GHD .Study design Serum insulin-like growth factor-1 (IGF-l)level was measured in 15 GHD children before and after 3 months of rhGH therapy and in 30 normal children. Oral glucose tolerance test(OGTT) and insulin releasing test(IRT) were performed before and after 3 months of rhGH therapy in 15 patients. Venous blood was sampled before and 30minutes, 60minutes, 120minutes after glucose load for measurements of plasma glucose and insulin. Insulin areas under the curve(AUCinsulin)[0 to 120 minutes] as well as glucose areas under the curve (AUCglucose)[0 to 120minutes] were calculated according to the trapezoid rule. The formula for the homeostasis model assessment(Homa) is as follows: Homa insulin resistance (Homa IR)= fasting insulin(uU/ml) X fasting plasma glucose (mmol/1) 722.5.Methods The serum IGF-1 concentration was measured by specific radioimmunoassays(RIA). Plasma glucose was measured by a glucose oxidase method with a glucose analyzer. Plasma insulin was determined by the electrochemiluminescence immunoassay on the Elecsys 1010 immunoassay analyzer. All calculation were performed with SPSS 10.0. Data are expressed as means ±SD. The Paired- Samples T test was used to compare data before and after treatment. Correlation analysis were performed using pearson correlation coefficient(r). Statistical analysis for comparison of data between groups was performed by the Student-Newman-Keuls.Results The growth velocities increased from 2.90 ± 0.7 cm/year before treatment to13.2± 3.5 cm/year after treatment (P<0.01). The levels of serum IGF-1 was significantly increased from117.38±24.12ug/ml to 266.05±48.30ug/ml (P<0.05). The levels of IGF-1 was correlated positively to the growth velocity before treatment (r=0.776 ; P<0.01)and negatively to the growth velocity after 3 months treatment(r= -0.84;P<0.01). OGTT were normal in 15 patients before treatment. After 3 months of rhGH therapy, fasting plasma glucose remained unchanged, but PG30min (P<0.01) , PGlh(P<0.05 ) , PG2h (P<0.05 ) and glucose areas under the curve (AUCglucose) P<0.01) increased significantly. Although a upward displacement of the glucose curve after rhGH treatment was observed, Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were not found in all patients. Fasting insulin (P<0.05 ) , INS30min( P<0.05 ) , INSlh ( P<0.01 ) , INS2h ( P<0.01 ) , insulin areas under the curve(AUCinsulin) (P<0.01) all increased significantly. The Homa IR increased from 1.51 ± 0.56 uU/ml X mmol/L before treatment to 2.13 ± 0.73uU/ml X mmol/L after treatment (P<0.05).Conclusion The replacement therapy of rhGH in GHD children are effective. The measurement of IGF-1 level may serve as useful parameters in the diagnosis of GHD and in the predicting effects of rhGH therapy. rhGH replacement therapy in GHD children in short period induced deterioration in insulin sensitivity and glucose tolerance. It's necessary to monitor PG and INS during rhGH replacement therapy.Postgraduate: Liang Jintao (pediatrics) Directed by Professor Li Tang...